Scleroderma is a serious disease characterized by excessible accumulation of collagen and other connective tissue components in skin and internal organs. The mechanisms responsible for such accumulation are not known. We will investigate the biochemical characteristics of skin obtained from normals and from patients with scleroderma to determine the nature of the biochemical abnormality. Biosynthesis of collagen in skin organ cultures and tissue cultures from dermal fibroblasts will be examined and the biosynthesized products will be characterized. Differences in the content or structure of the various components present in the tissues or synthesized in the cultures will be identified. Special emphasis will be placed on the identification of the various collagen types present and in the quantitation of their relative proportions. The effects of various cellular and humoral components obtained from patients with scleroderma on the biosynthesis and function of fibroblasts and endothelial cells in culture will be examined to identify factors responsible for the massive connective tissue accumulation. At the present, there is no adequate therapy for scleroderma and the disease progresses relentlessly. We propose a novel approach based on the pharmacological manipulation of the various steps required for synthesis of collagen to attain specific or selective inhibition of connective tissue accumulation. This approach will result in the identification of possible therapeutic agents which may be beneficial in preventing progression of the disease.